Int. J. Mol. Sci. 2012, 13(6), 6983-6994; doi:10.3390/ijms13066983
Article

O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions

Claire Villalva 1,2,† email, Ulrich Cortes 1,2,† email, Michel Wager 3 email, Jean-Marc Tourani 4 email, Pierre Rivet 2 email, Celine Marquant 2 email, Sebastien Martin 2 email, Ali G. Turhan 1,2 email and Lucie Karayan-Tapon 1,2,* email
1 INSERM U935, University of Poitiers, Poitiers F-86021, France 2 Department of Hematology and Oncology, University Hospital of Poitiers, University of Poitiers, Poitiers F-86021, France 3 Department of Neurosurgery, University Hospital of Poitiers, University of Poitiers, Poitiers F-86021, France 4 Department of Medical Oncology, University Hospital of Poitiers, University of Poitiers, Poitiers F-86021, France † These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 7 April 2012; in revised form: 25 May 2012 / Accepted: 1 June 2012 / Published: 7 June 2012
(This article belongs to the Special Issue Advances in Molecular Oncology)
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Abstract: Glioblastoma (GBM) is the most malignant type of primary brain tumor with a very poor prognosis. The actual standard protocol of treatment for GBM patients consists of radiotherapy and concomitant temozolomide (TMZ). However, the therapeutic efficacy of this treatment is limited due to tumor recurrence and TMZ resistance. Recently isolated, glioma stem-like cells (GSCs) are thought to represent the population of tumorigenic cells responsible for GBM resistance and recurrence following surgery and chemotherapy. In addition, MGMT (O6-methylguanine-methyltransferase) methylation is considered as one of the principal mechanisms contributing to TMZ sensitivity of GBM. In this study we have isolated GSCs from 10 adult GBM patients and investigated the relationship between MGMT methylation status and Temozolomide (TMZ) sensitivity of these lines grown either in stem-like or differentiation promoting conditions. Sensitivity to TMZ was significantly associated with MGMT methylation status in cells committed to differentiation but not in stem-like cells. In addition, patients harboring highly methylated MGMT promoters had a longer overall survival. These results reveal the importance of the differentiation process when considering the predictive value of MGMT status in GSCs for clinical response to TMZ.
Keywords: MGMT methylation; glioma stem-like cells; temozolomide; differentiation

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MDPI and ACS Style

Villalva, C.; Cortes, U.; Wager, M.; Tourani, J.-M.; Rivet, P.; Marquant, C.; Martin, S.; Turhan, A.G.; Karayan-Tapon, L. O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions. Int. J. Mol. Sci. 2012, 13, 6983-6994.

AMA Style

Villalva C, Cortes U, Wager M, Tourani J-M, Rivet P, Marquant C, Martin S, Turhan AG, Karayan-Tapon L. O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions. International Journal of Molecular Sciences. 2012; 13(6):6983-6994.

Chicago/Turabian Style

Villalva, Claire; Cortes, Ulrich; Wager, Michel; Tourani, Jean-Marc; Rivet, Pierre; Marquant, Celine; Martin, Sebastien; Turhan, Ali G.; Karayan-Tapon, Lucie. 2012. "O6-Methylguanine-Methyltransferase (MGMT) Promoter Methylation Status in Glioma Stem-Like Cells is Correlated to Temozolomide Sensitivity Under Differentiation-Promoting Conditions." Int. J. Mol. Sci. 13, no. 6: 6983-6994.

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